Sorafenib might prolong survival in individuals with advanced hepatocellular carcinoma (HCC), but with limited efficacy. whole cohort were 10.5 [95% confidence interval (CI), 8.7C12.3] and 5.0 months (95% CI, 3.7C6.3), respectively. Sorafenib in combination with local therapy was an independent predictor for longer PFS, whereas Eastern Cooperative Group (ECOG) overall performance status (PS) and Child-Pugh class were associated with reduced PFS. Local therapy was associated with longer OS while ECOG PS and -fetoprotein were associated with reduced OS. Inside a subset of individuals with radiological progressive disease, a significant difference was found in OS between individuals who continued taking sorafenib and those who discontinued therapy (11 vs. 7.5 months, P<0.001). In conclusion, sorafenib in combination with local therapy (transarterial chemoembolization with/without cryoablation) was individually associated with longer OS and PFS in advanced HCC individuals. Poor ECOG PS was associated with shorter OS and PFS and is therefore a marker of poor results in sorafenib-treated HCC individuals. (10), it was found that pretreatment tumor phosphorylated ERK levels were correlated with TTP. However, in individuals with advanced HCC who are amenable only to systemic therapy, tumor cells is generally not available as needle tract metastases may arise from biopsy, hindering further efforts to understand the molecular biology of tumor resistance to therapy. A more recent phase II open-label study carried out by Yau (11) exposed that the presence of lung metastasis was a poor prognostic element and implied that a high tumor weight may render the individuals refractory to sorafenib treatment. In the mean time, Vincenzi (12) reported that early pores and skin toxicity Rabbit Polyclonal to APLP2. may be a predictive element for tumor control in HCC individuals treated with sorafenib. Despite these reports, it remains unclear whether the established prognostic factors, MLN8237 including Child-Pugh classification, -fetoprotein (AFP), portal vein thrombosis (PVT), hepatitis B virus (HBV) DNA and tumor differentiation and size, are relevant to patients treated with sorafenib. Therefore, the aim of this study was to prospectively investigate the efficacy and determine the prognostic factors for progression-free survival (PFS) and OS MLN8237 in patients with advanced HBV-related HCC treated with sorafenib as first-line therapy. Materials and methods Patients Based on the BCLC staging classification, 326 consecutive patients with HBV-related advanced HCC were screened between August 2008 and May 2010 at the Center of Therapeutic Research for Hepatocellular Carcinoma, Beijing 302nd Hospital (Beijing, China). A total of 67 patients were Child-Pugh C, 58 patients were Child-Pugh B8 or B9 with serum bilirubin level >51.3 mol/l. A total of 91 patients had a history of either hepatectomy (14), preoperative chemotherapy (11), prior TACE or local ablation (47) or radiotherapy (19). As a result, 216 patients were excluded from the analyses and 110 patients were included in the present study (Table I). HCC was diagnosed based on a serum AFP level >400 ng/ml and typical imaging findings consistent with the criteria of the European Association for the Study of the Liver (13). Liver biopsies were obtained in 58 patients with uncertain diagnosis and assessed histologically to confirm diagnosis. The BCLC classification was used to identify tumor stages (14). The presence of PVT, representing macroscopic vascular invasion and extrahepatic spread, was used to define advanced HCC. Performance status (PS) was evaluated according to the Eastern Cooperative Oncology Group criteria. Patients who met the following criteria were included in the study: diagnosis of advanced HCC, first-line treatment with sorafenib, ECOG PS 2, Child-Pugh class A or B and total serum bilirubin level <51.3 mol/l, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels less than five times the normal upper limit, adequate hematological function (platelet count greater than 50109/l and hemoglobin level more than 80 g/l) and adequate renal function (serum creatinine level less than 1.5 times the normal upper limit). MLN8237 Baseline demographic, clinical and laboratory data were collected for all patients using a uniform database template to ensure consistent data collection. Outcomes, including PFS and OS, were collected from patient charts. All treatments were approved by the Beijing 302nd Hospital Research Ethics Committee, and written informed consent was obtained from the patients who met the inclusive criteria prior to the collection of data and blood and tumor specimens and analysis being performed. Table I. Patient characteristics (n=110). Sorafenib administration All the patients received sorafenib. The dosage was 400 mg twice daily (the standard dose); treatment interruptions and dose reductions (first 400 mg double daily,.